RESUMEN
Comprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.
Asunto(s)
Comunicación Autocrina , Proteínas Tirosina Quinasas Receptoras/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Animales , Línea Celular Tumoral , Bases de Datos Factuales , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Estimación de Kaplan-Meier , Ratones , Invasividad Neoplásica , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Trasplante Heterólogo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidad , Tirosina Quinasa del Receptor AxlRESUMEN
OBJECTIVE: The purpose of this review is to ascertain the indications, techniques, and the associated morbidity with the use of Bakri balloon. MATERIAL AND METHODS: A literature search using the PubMed database was conducted from 2001 to 2013. We calculated 95% confidence intervals (CIs) for complications. RESULTS: We identified 12 publications that met the inclusion criteria. Four reports provided the frequency of Bakri use during the study period, with the overall rate being 0.20% (138/69, 174; 95% CI, 0.17-0.25%). Two-thirds of use followed cesarean delivery (67%; 182/273). Uterine atony was specified as the underlying etiology of postpartum hemorrhage in 75% (9/12) of publication. The rate of balloon displacement was 10% (95% CI, 6-16%) and need for transfusion, 43% (95% CI, 32-55%). Hysterectomy was undertaken in 6% (95% CI, 4-10%). CONCLUSIONS: There is a paucity of publications on Bakri balloon. Before its utilization is recommended in guidelines, a randomized clinical trial comparing uterotonics alone versus with balloon is warranted.